Studies toward the total synthesis of ingenol

Ingenol, 1, is a tetracyclic diterpene isolated from various species of the Euphorbiaceae plant family. Due to its intriguing biological activity and structural complexity, the total synthesis of ingenol was eagerly pursued.* This dissertation describes the synthetic efforts toward ingenol highlighting the [2+2+1] Pauson-Khand cyclization and the [2+2] olefin-dioxenone photocycloaddition/retroaldol fragmentation methodology. An expedient 9-step synthesis of the ABC tricyclic carboskeleton of ingenol with out,out-stereochemistry was developed. Encouraging investigations toward the preparation of the in,out-isomer are also described. A novel cyclization of 1,6-enynes bearing 3,4-dioxenone functionality to cycloheptatrienes was discovered. In addition, the stereoselectivity of the Pauson-Khand cyclization of various 1,6-enynes was determined and working models proposed. *Please refer to dissertation for diagrams